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Toxins, Volume 10, Issue 7 (July 2018)

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Open AccessFeature PaperReview Bioengineering of Bordetella pertussis Adenylate Cyclase Toxin for Antigen-Delivery and Immunotherapy
Toxins 2018, 10(7), 302; https://doi.org/10.3390/toxins10070302 (registering DOI)
Received: 6 July 2018 / Revised: 16 July 2018 / Accepted: 18 July 2018 / Published: 20 July 2018
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Abstract
The adenylate cyclase toxin (CyaA) is one of the major virulence factors of Bordetella pertussis, the causative agent of whooping cough. CyaA is able to invade eukaryotic cells where, upon activation by endogenous calmodulin, it synthesizes massive amounts of cAMP that alters
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The adenylate cyclase toxin (CyaA) is one of the major virulence factors of Bordetella pertussis, the causative agent of whooping cough. CyaA is able to invade eukaryotic cells where, upon activation by endogenous calmodulin, it synthesizes massive amounts of cAMP that alters cellular physiology. The CyaA toxin is a 1706 residues-long bifunctional protein: the catalytic domain is located in the 400 amino-proximal residues, whereas the carboxy-terminal 1306 residues are implicated in toxin binding to the cellular receptor, the αMβ2 (CD11b/CD18) integrin, and subsequently in the translocation of the catalytic domain across the cytoplasmic membrane of the target cells. Indeed, this protein is endowed with the unique capability of delivering its N-terminal catalytic domain directly across the plasma membrane of eukaryotic target cells. These properties have been exploited to engineer the CyaA toxin as a potent non-replicating vector able to deliver antigens into antigen presenting cells and elicit specific cell-mediated immune responses. Antigens of interest can be inserted into the CyaA protein to yield recombinant molecules that are targeted in vivo to dendritic cells, where the antigens are processed and presented by the major class I and class II histocompatibility complexes (MHC-I and II). CyaA turned out to be a remarkably effective and versatile vaccine vector capable of inducing all the components of the immune response (T-CD4, T-CD8, and antibody). In this chapter, we summarize the basic knowledge on the adenylate cyclase toxin and then describe the application of CyaA in vaccinology, including some recent results of clinical trials of immunotherapy using a recombinant CyaA vaccine. Full article
(This article belongs to the Special Issue Adenylate Cyclase (CyaA) Toxin)
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Open AccessArticle The PHD Transcription Factor Rum1 Regulates Morphogenesis and Aflatoxin Biosynthesis in Aspergillus flavus
Received: 8 June 2018 / Revised: 16 July 2018 / Accepted: 18 July 2018 / Published: 20 July 2018
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Abstract
Aspergillus flavus produces mycotoxins especially aflatoxin B1 and infects crops worldwide. As a PHD transcription factor, there is no report on the role of Rum1 in the virulence of Aspergillus spp. yet. This study explored the biological function of Rum1 in A.
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Aspergillus flavus produces mycotoxins especially aflatoxin B1 and infects crops worldwide. As a PHD transcription factor, there is no report on the role of Rum1 in the virulence of Aspergillus spp. yet. This study explored the biological function of Rum1 in A. flavus through the construction of rum1 deletion mutants and rum1 complementation strains with the method of homologous recombination. It was found, in the study, that Rum1 negatively regulates conidiation through abaA and brlA, positively regulates sclerotia formation through nsdC, nsdD, and sclR, triggers aflatoxin biological synthesis, and enhances the activity of amylase. Our findings suggested that Rum1 plays a major role in the growth of mycelia, conidia, and sclerotia production along with aflatoxin biosynthesis in A. flavus. Full article
(This article belongs to the collection Aflatoxins)
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Open AccessReview Impact of Altered Intestinal Microbiota on Chronic Kidney Disease Progression
Received: 15 June 2018 / Revised: 13 July 2018 / Accepted: 17 July 2018 / Published: 19 July 2018
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Abstract
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl
[...] Read more.
In chronic kidney disease (CKD), accumulation of uremic toxins is associated with an increased risk of CKD progression. Some uremic toxins result from nutrient processing by gut microbiota, yielding precursors of uremic toxins or uremic toxins themselves, such as trimethylamine N-Oxide (TMAO), p-cresyl sulphate, indoxyl sulphate and indole-3 acetic acid. Increased intake of some nutrients may modify the gut microbiota, increasing the number of bacteria that process them to yield uremic toxins. Circulating levels of nutrient-derived uremic toxins are associated to increased risk of CKD progression. This offers the opportunity for therapeutic intervention by either modifying the diet, modifying the microbiota, decreasing uremic toxin production by microbiota, increasing toxin excretion or targeting specific uremic toxins. We now review the link between nutrients, microbiota and uremic toxin with CKD progression. Specific focus will be placed on the generation specific uremic toxins with nephrotoxic potential, the decreased availability of bacteria-derived metabolites with nephroprotective potential, such as vitamin K and butyrate and the cellular and molecular mechanisms linking these toxins and protective factors to kidney diseases. This information provides a conceptual framework that allows the development of novel therapeutic approaches. Full article
(This article belongs to the Special Issue The Intestine and Uremia)
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Open AccessFeature PaperArticle Botulinum Toxin for the Treatment of Hand Tremor
Received: 26 June 2018 / Revised: 14 July 2018 / Accepted: 15 July 2018 / Published: 19 July 2018
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Abstract
The aim of this study is to review our longitudinal experience with onabotulinumtoxinA (onaBoNT-A) injections for medically refractory hand tremor. We performed a retrospective review of our database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at
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The aim of this study is to review our longitudinal experience with onabotulinumtoxinA (onaBoNT-A) injections for medically refractory hand tremor. We performed a retrospective review of our database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at least 2 sessions with follow-up. The majority were injected into the forearm flexors (FF), although treatment was individualized. During the specified period, 91 patients (53 essential tremor, 31 dystonic tremor, 6 Parkinson’s disease tremor, and 1 cerebellar outflow tremor) met our inclusion criteria. The mean age (SD) was 64.8 years (12.8), and mean duration of follow-up was 29.6 months (25.1) with mean of 7.7 (6.3) treatment visits. FF were injected in 89 (97.8%) patients, exclusively in 74 (81.3%), and 15 (16.5%) were injected in FF and other muscles. EMG guidance was used in 5 patients (5.5%). On a 0–4 “peak effect” rating scale (0 = no effect, 4 = marked improvement in severity and function), 80.2% and 85.7% of patients reported moderate or marked improvement (score 3 or 4) at their first and last follow-up visit, respectively. There was no statistically significant difference in the outcomes between first and last visit: average “peak effect” rating score (3.2 versus 3.4), “global” rating score (3.0 versus 3.2), latency of response (4.5 versus 3.8 days), and total duration of response (12.7 versus 12.8 weeks), except onaBoNT-A dose (65.0 versus 78.6 U/limb, p = 0.002). Of 1095 limb injections, there were 134 (12.2%) non-disabling and transient (mean 36 days) adverse events (132 limb weakness, 2 pain). OnaBoNT-A injections are safe and effective in the treatment of hand tremor. Full article
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Open AccessReview Intestinal Barrier Function in Chronic Kidney Disease
Received: 29 June 2018 / Revised: 16 July 2018 / Accepted: 18 July 2018 / Published: 19 July 2018
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Abstract
The kidneys are key contributors to body homeostasis, by virtue of controlled excretion of excessive fluid, electrolytes, and toxic waste products. The syndrome of uremia equals the altered physiology due to irreversible loss of kidney function that is left uncorrected for, despite therapeutic
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The kidneys are key contributors to body homeostasis, by virtue of controlled excretion of excessive fluid, electrolytes, and toxic waste products. The syndrome of uremia equals the altered physiology due to irreversible loss of kidney function that is left uncorrected for, despite therapeutic intervention(s). The intestines and its microbial content are prime contributors to this syndrome. The intestinal barrier separates the self (or the so-called “milieu intérior”) from the environment. In the large intestine, the intestinal barrier keeps apart human physiology and the microbiota. The enterocytes and the extracellular mucin layer functions form a complex multilayered structure, facilitating complex bidirectional metabolic and immunological crosstalk. The current review focuses on the intestinal barrier in chronic kidney disease (CKD). Loss of kidney function results in structural and functional alterations of the intestinal barrier, contribution to the syndrome of uremia. Full article
(This article belongs to the Special Issue The Intestine and Uremia)
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Open AccessFeature PaperArticle Differential Toxicity of Cyanobacteria Isolated from Marine Sponges towards Echinoderms and Crustaceans
Received: 28 May 2018 / Revised: 15 July 2018 / Accepted: 16 July 2018 / Published: 18 July 2018
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Abstract
Marine sponges and cyanobacteria have a long history of co-evolution, with documented genome adaptations in cyanobionts. Both organisms are known to produce a wide variety of natural compounds, with only scarce information about novel natural compounds produced by cyanobionts. In the present study,
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Marine sponges and cyanobacteria have a long history of co-evolution, with documented genome adaptations in cyanobionts. Both organisms are known to produce a wide variety of natural compounds, with only scarce information about novel natural compounds produced by cyanobionts. In the present study, we aimed to address their toxicological potential, isolating cyanobacteria (n = 12) from different sponge species from the coast of Portugal (mainland, Azores, and Madeira Islands). After large-scale growth, we obtained both organic and aqueous extracts to perform a series of ecologically-relevant bioassays. In the acute toxicity assay, using nauplii of Artemia salina, only organic extracts showed lethality, especially in picocyanobacterial strains. In the bioassay with Paracentrotus lividus, both organic and aqueous extracts produced embryogenic toxicity (respectively 58% and 36%), pointing to the presence of compounds that interfere with growth factors on cells. No development of pluteus larvae was observed for the organic extract of the strain Chroococcales 6MA13ti, indicating the presence of compounds that affect skeleton formation. In the hemolytic assay, none of the extracts induced red blood cells lysis. Organic extracts, especially from picoplanktonic strains, proved to be the most promising for future bioassay-guided fractionation and compounds isolation. This approach allows us to classify the compounds extracted from the cyanobacteria into effect categories and bioactivity profiles. Full article
(This article belongs to the Special Issue Cyanobacteria and Cyanotoxins: New Advances and Future Challenges)
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Open AccessArticle Biomarker Evaluation and Toxic Effects of an Acute Oral and Systemic Fumonisin Exposure of Pigs with a Special Focus on Dietary Fumonisin Esterase Supplementation
Received: 29 May 2018 / Revised: 4 July 2018 / Accepted: 15 July 2018 / Published: 17 July 2018
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Abstract
The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed. It causes a disruption of sphingolipid metabolism and pulmonary, hepatic, and immunological lesions in pigs depending on the exposure scenario. One sensitive biomarker for FB1 exposure is the sphinganine (Sa) to sphingosine
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The mycotoxin fumonisin B1 (FB1) is a frequent contaminant of feed. It causes a disruption of sphingolipid metabolism and pulmonary, hepatic, and immunological lesions in pigs depending on the exposure scenario. One sensitive biomarker for FB1 exposure is the sphinganine (Sa) to sphingosine (So) ratio in blood. The fumonisin esterase FumD, which can be used as a feed additive, converts FB1 into the much less toxic metabolite hydrolyzed FB1 (HFB1). We conducted a single-dose study with barrows allocated to one of five treatments: (1) control (feed, 0.9% NaCl intravenously iv), (2) 139 nmol FB1 or (3) HFB1/kg BW iv, (4) 3425 nmol FB1/kg BW orally (po), or (5) 3321 nmol FB1/kg BW and 240 U FumD/kg feed po. The Sa/So ratio of iv and po FB1 administered groups was significantly elevated in blood and Liquor cerebrospinalis, but no fumonisin-associated differences were reflected in other endpoints. Neither clinical lung affections nor histopathological pulmonary lesions were detected in either group, while some parameters of hematology and clinical biochemistry showed a treatment–time interaction. FumD application resulted in Sa/So ratios comparable to the control, indicating that the enzymatic treatment was effectively preventing the fumonisin-induced disruption of sphingolipid metabolism. Full article
(This article belongs to the collection Fusarium Toxins – Relevance for Human and Animal Health)
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Open AccessArticle Unilateral Botulinum Neurotoxin-A Injection into the Striatum of C57BL/6 Mice Leads to a Different Motor Behavior Compared with Rats
Received: 5 July 2018 / Revised: 13 July 2018 / Accepted: 15 July 2018 / Published: 17 July 2018
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Abstract
Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A
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Different morphological changes in the caudate-putamen (CPu) of naïve rats and mice were observed after intrastriatal botulinum neurotoxin-A (BoNT-A) injection. For this purpose we here studied various motor behaviors in mice (n = 46) longitudinally up to 9 months after intrastriatal BoNT-A administration as previously reported for rats, and compared both outcomes. Apomorphine- and amphetamine-induced rotational behavior, spontaneous motor behavior, as well as lateralized neglect were studied in mice after the injection of single doses of BoNT-A into the right CPu, comparing them with sham-injected animals. Unilateral intrastriatal injection of BoNT-A in mice induced significantly increased contralateral apomorphine-induced rotations for 1 to 3 months, as well as significantly increased contralateral amphetamine-induced rotations 1 to 9 months after injection. In rats (n = 28), unilateral BoNT-A injection also induced significantly increased contralateral apomorphine-induced rotations 3 months after injection, but did not provoke amphetamine-induced rotations at all. Lateralized sensorimotor integration, forelimb preference, and forelimb stepping were significantly impaired on the left side. The differences in motor behaviors between rats and mice may be caused by different BoNT-A effects on cholinergic and catecholaminergic fibers in rat and mouse striata, interspecies differences in striatal receptor densities, and different connectomes of the basal ganglia. Full article
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Open AccessArticle Multi-Mycotoxin Occurrence in Dairy Cattle Feeds from the Gauteng Province of South Africa: A Pilot Study Using UHPLC-QTOF-MS/MS
Received: 4 June 2018 / Revised: 25 June 2018 / Accepted: 4 July 2018 / Published: 16 July 2018
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Abstract
The indispensable nature of toxigenic fungi and mycotoxins in agricultural systems is of worldwide concern, hence the need for surveillance studies to preserve public health. Thirteen dairy farms were surveyed and 40 dairy feeds of varying nature collected and analyzed for mycotoxins. Estimated
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The indispensable nature of toxigenic fungi and mycotoxins in agricultural systems is of worldwide concern, hence the need for surveillance studies to preserve public health. Thirteen dairy farms were surveyed and 40 dairy feeds of varying nature collected and analyzed for mycotoxins. Estimated levels of aflatoxins (AFs), fumonisin B1 (FB1), ochratoxin A (OTA), citrinin (CIT), zearalenone (ZEN), α-zearalenol (α-ZEL), β-zearalenol (β-ZEL), deoxynivalenol (DON), 3- and 15-acetyl-deoxynivalenol (ADONs), HT-2 toxin (HT-2), and beauvericin (BEA) were established using liquid chromatography-tandem mass spectrometry. Highest frequencies (40/40) were found for AFG2 (range: <LOQ—116.1 ppb), α-ZEL (range: 0.98–13.24 ppb), and β-ZEL (range: 0.73–4.71 ppb), followed by AFB2 at 37/40 (range: <LOQ—23.88 ppb), BEA at 36/40 (range: <LOQ—55.99 ppb), HT-2 at 35/40 (range: <LOQ—312.95 ppb), and FB1 at 34/40 (range: <LOQ—1389.62 ppb). Apart from samples exceeding regulatory limits for total AFs in dairy feeds due to the high amounts of AFG2 and AFB2, levels of other mycotoxins were regarded as safe for dairy production in South Africa. This is the first-time the natural occurrence of the cold climate HT-2 in South African feeds was documented. Persistent co-occurrence of multiple mycotoxins across samples, however, may elicit synergistic and/or additive effects in hosts, hence raising concerns about their impacts and how such interactions may affect the dairy livestock sector. Full article
(This article belongs to the collection Understanding Mycotoxin Occurrence in Food and Feed Chains)
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Open AccessArticle Characterisation of the Mycobiota on the Shell Surface of Table Eggs Acquired from Different Egg-Laying Hen Breeding Systems
Received: 14 June 2018 / Revised: 12 July 2018 / Accepted: 14 July 2018 / Published: 16 July 2018
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Abstract
Microbial safety is an important factor contributing to the egg quality. During egg acquisition, there is significant risk of contamination of the eggshell surface with microscopic fungi. Mycelial hyphae may grow on the eggshell surface and penetrate into the egg content. However, there
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Microbial safety is an important factor contributing to the egg quality. During egg acquisition, there is significant risk of contamination of the eggshell surface with microscopic fungi. Mycelial hyphae may grow on the eggshell surface and penetrate into the egg content. However, there is no information on the populations of microscopic fungi on the eggshell surface and, consequently, on possible production of mycotoxins. Therefore, the aim of the study was to identify the species of microscopic fungi present on the eggshell surface acquired from different breeding systems and to measure the number of selected mycotoxins. The qualitative analysis resulted in the identification of 41 isolates on the surface of eggs. There were 7 isolates from the organic production system, 11 from the free-range production system, 14 from the deep litter indoor housing system and 9 from the cage farming production system. The research proved that the diversification in the population of mycobiota on the eggshells depended on the egg-laying hen breeding system. The microscopic fungi isolated from the eggshells included toxigenic and pathogenic species such as Fusarium culmorum and F. equiseti. As the egg storage time increased, fungi, including the pathogenic species, penetrated through the eggshells. In consequence, mycotoxins were identified in the egg whites. Type-A and type-B trichothecenes were found in the eggshell samples containing F. culmorum. Full article
(This article belongs to the Section Mycotoxins)
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Open AccessReview Studying Smaller and Neglected Organisms in Modern Evolutionary Venomics Implementing RNASeq (Transcriptomics)—A Critical Guide
Received: 25 June 2018 / Revised: 6 July 2018 / Accepted: 13 July 2018 / Published: 16 July 2018
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Abstract
Venoms are evolutionary key adaptations that species employ for defense, predation or competition. However, the processes and forces that drive the evolution of venoms and their toxin components remain in many aspects understudied. In particular, the venoms of many smaller, neglected (mostly invertebrate)
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Venoms are evolutionary key adaptations that species employ for defense, predation or competition. However, the processes and forces that drive the evolution of venoms and their toxin components remain in many aspects understudied. In particular, the venoms of many smaller, neglected (mostly invertebrate) organisms are not characterized in detail, especially with modern methods. For the majority of these taxa, even their biology is only vaguely known. Modern evolutionary venomics addresses the question of how venoms evolve by applying a plethora of -omics methods. These recently became so sensitive and enhanced that smaller, neglected organisms are now more easily accessible to comparatively study their venoms. More knowledge about these taxa is essential to better understand venom evolution in general. The methodological core pillars of integrative evolutionary venomics are genomics, transcriptomics and proteomics, which are complemented by functional morphology and the field of protein synthesis and activity tests. This manuscript focuses on transcriptomics (or RNASeq) as one toolbox to describe venom evolution in smaller, neglected taxa. It provides a hands-on guide that discusses a generalized RNASeq workflow, which can be adapted, accordingly, to respective projects. For neglected and small taxa, generalized recommendations are difficult to give and conclusions need to be made individually from case to case. In the context of evolutionary venomics, this overview highlights critical points, but also promises of RNASeq analyses. Methodologically, these concern the impact of read processing, possible improvements by perfoming multiple and merged assemblies, and adequate quantification of expressed transcripts. Readers are guided to reappraise their hypotheses on venom evolution in smaller organisms and how robustly these are testable with the current transcriptomics toolbox. The complementary approach that combines particular proteomics but also genomics with transcriptomics is discussed as well. As recently shown, comparative proteomics is, for example, most important in preventing false positive identifications of possible toxin transcripts. Finally, future directions in transcriptomics, such as applying 3rd generation sequencing strategies to overcome difficulties by short read assemblies, are briefly addressed. Full article
(This article belongs to the Section Animal Venoms)
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Open AccessArticle Label-Free Optical Detection of Mycotoxins Using Specific Aptamers Immobilized on Gold Nanostructures
Received: 26 June 2018 / Revised: 12 July 2018 / Accepted: 13 July 2018 / Published: 16 July 2018
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Abstract
This work focuses on the development of the novel label-free optical apta-sensors for detection of mycotoxins. A highly sensitive analytical method of total internal reflection ellipsometry (TIRE) combined with Localized Surface Plasmon Resonance (LSPR) phenomenon in nano-structured gold films was exploited here for
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This work focuses on the development of the novel label-free optical apta-sensors for detection of mycotoxins. A highly sensitive analytical method of total internal reflection ellipsometry (TIRE) combined with Localized Surface Plasmon Resonance (LSPR) phenomenon in nano-structured gold films was exploited here for the first time for detection of aflatoxin B1 and M1 in direct assay with specific aptamers immobilized on the surface of gold. The achieved detection of low molecular weight molecules, such as aflatoxin B1 and M1, in a wide range of concentrations from 100 ng/mL down to 0.01 ng/mL is remarkable for the LSPR method. The study of binding kinetics of aflatoxin molecules to their respective aptamers using dynamic TIRE measurements yielded the values of affinity constants in the range of 10−8–10−7 mol, which is characteristic for highly specific aptamer/target interactions similar to that for monoclonal antibodies. The effect of aptamers’ DNA chain length on their binding characteristics was analyzed. Full article
(This article belongs to the Special Issue Advanced Sensors for Toxins)
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Open AccessArticle The Effect of Cyanobacterial LPS Antagonist (CyP) on Cytokines and Micro-RNA Expression Induced by Porphyromonas gingivalis LPS
Received: 14 June 2018 / Revised: 6 July 2018 / Accepted: 11 July 2018 / Published: 16 July 2018
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Abstract
Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is
[...] Read more.
Lipopolysaccharide (LPS) from Porphyromonas gingivalis (Pg-LPS) is a key bacterial structure involved in the maintenance of a chronic pro-inflammatory environment during periodontitis. Similar to other gram-negative LPS, Pg-LPS induces the release of pro-inflammatory cytokines through interaction with Toll-Like Receptor 4 (TLR4) and is able to stimulate negative TLR4 regulatory pathways, such as those involving microRNA (miRNA). In this work, we employed CyP, an LPS with TLR4-MD2 antagonist activity obtained from the cyanobacterium Oscillatoria planktothrix FP1, to study the effects on pro-inflammatory cytokine production and miRNA expression in human monocytic THP-1 cells stimulated with Pg-LPS or E. coli LPS (Ec-LPS). Results showed that CyP inhibited TNF-α, IL-1β and IL-8 expression more efficiently when co-incubated with Pg-LPS rather than with Ec-LPS. The inhibition of pro-inflammatory cytokine production was maintained even when CyP was added 2 h after LPS. The analysis of the effects of CyP on miRNA expression showed that, although being an antagonist, CyP did not inhibit miR-146a induced by Pg-LPS or Ec-LPS, whereas it significantly inhibited miR-155 only in the cultures stimulated with Ec-LPS. These results suggest that CyP may modulate the pro-inflammatory response induced by Pg-LPS, not only by blocking TLR4-MD2 complex, but also by preserving miR-146a expression. Full article
(This article belongs to the Special Issue Lipopolysaccharide: Bacterial Endotoxin)
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Open AccessArticle Establishment of a New Zealand White Rabbit Model for Lethal Toxin (LT) Challenge and Efficacy of Monoclonal Antibody 5E11 in the LT-Challenged Rabbit Model
Received: 15 June 2018 / Accepted: 9 July 2018 / Published: 12 July 2018
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Abstract
Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11
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Anthrax caused by Bacillus anthracis is a lethal infectious disease, especially when inhaled, and the mortality rate approaches 100% without treatment. The anthrax antitoxin monoclonal antibody (MAb) 5E11 is a humanized antibody that targets the anthrax protective antigen (PA). The efficacy of 5E11 needs proper animal models. However, anthrax spores are extremely dangerous, so experiments must be conducted under Biosafety Level 3 conditions. Considering the critical effects of lethal toxin (LT) on hosts during infection, we report the establishment of a LT-challenged rabbit model, which caused 100% mortality with a dose of 2 mg PA + 1 mg LF, while a 4 mg PA + 2 mg LF challenge could limit death to within three days. Then, we evaluated 5E11 efficacy against LT. A prophylactic study showed that the i.v. administration of 40 mg/kg 5E11 four days before lethal dose LT challenge could lead to 100% survival. In therapeutic studies, the i.v. administration of 40 mg/kg 5E11 10 min after lethal dose LT challenge could provide complete protection. Overall, we developed a new LT-challenged rabbit model, and our results indicate that 5E11 shows potential for the clinical application in anthrax treatment. Full article
(This article belongs to the collection Anthrax Toxins)
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Open AccessArticle Detection of the Potential Inactivation of Tetrodotoxin by Lactic Acid Bacterial Exopolysaccharide
Received: 8 June 2018 / Revised: 2 July 2018 / Accepted: 2 July 2018 / Published: 12 July 2018
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Abstract
Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau
[...] Read more.
Screening for compounds that can neutralize the toxicity of tetrodotoxin (TTX) or reduce its negative effects is necessary. Our study tested the TTX detoxification capacity of exopolysaccharide (EPS) extracted from lactic acid bacteria. EPS of Leuconostoc mesenteroides N3 isolated from the Vung Tau sea (Vietnam), Lactobacillus plantarum PN05, and Lactobacillus rhamnosus PN04 were used in the study. To more completely evaluate the importance of EPS in detoxification, EPS samples of Leuconostoc mesenteroides N3, Lactobacillus plantarum PN05 and Lactobacillus rhamnosus PN04 were also tested. The majority of EPS of these bacteria contained glucose; this was observed using thin layer chromatography (TLC) and high-performance liquid chromatography (HPLC) analysis. As observed with FTIR analysis, only EPS of Lactobacillus plantarum PN05 contained methyl groups. The results indicated that detoxification of TTX in mice could be obtained at an optimal dose of 248 µg EPS from Leuconostoc mesenteroides incubated with 54 µg cuprous oxide for 40 min or 148 µg EPS Lactobacillus rhamnosus incubated with 55 µg cuprous oxide for 40 min, while EPS from Lactobacillus plantarum showed TTX detoxification capacity without cuprous oxide combination. Consequently, EPS from Lactobacillus plantarum PN05 can be used in TTX prevention. This is the first report on the importance of lactic acid bacteria in TTX detoxification. Full article
(This article belongs to the Special Issue Tetrodotoxins)
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